Activation ratio of MMP-2 and expression of MT1-MMP are correlated in thymic epithelial tumours

SummaryAimsTo study the relationships between the activation of pro-MMP-2 and the mRNA levels of MT1-MMP and TIMP-2 in thymic tissues and thymic epithelial tumours.MethodsWe examined the mRNA expressions of MMP-2, MT1-MMP and TIMP-2 with real-time reverse transcription- polymerase chain reaction (RT-PCR). The gelatinolytic activity and MMP-2 activation ratio of thymic tissues, thymomas, and thymic carcinomas were determined with gelatin zymography. The cellular localisation of MMP-2 was detected with film in situ gelatin zymography. We then examined the mRNA expression of MMP-2 in the epithelial tumour cells or lymphocytes and stromal cells distant from the tumour (obtained from two invasive thymomas) using laser-capture microdissection (LCM).ResultsThe mRNA levels of MMP-2, MT1-MMP and TIMP-2 were significantly increased from thymic tissue, Stage I-II, III-IV thymomas to thymic carcinomas (p<0.005). They were also significantly increased from AB-B1 (lymphocyte rich and mixed types), B2-B3 (cortical and predominantly polygonal cells types) thymomas to thymic carcinomas (p<0.05). The MMP-2 activation ratio also had the same tendency among the above groups (p<0.05) and was directly correlated to MT1-MMP and TIMP-2 mRNA expression (Spearman rank correlation: r = 0.8627, r = 0.8314; p<0.005). Film in situ zymography demonstrated that positive expression is mainly localised in tumour cell nests and adjacent stroma cells. LCM and real-time RT-PCR results comfirmed that the expression of MMP-2 was higher in epithelial tumour cells than in lymphocytes and stromal cells.ConclusionsMMP-2, MT1-MMP and TIMP-2 mRNA expression levels were correlated with clinical stages and histological subtypes of thymic epithelial tumours. The activation of pro-MMP-2 might be mediated by MT1-MMP and TIMP-2 up- regulation.